Primary biliary cirrhosis (PBC) is a progressive liver disease believed to be of autoimmune nature. Its etiology is unknown. It is characterized by progressive intrahepatic cholestasis as a result of ongoing non-suppurative destructive cholangitis that affecting small intrahepatic bile ducts. It affects approximate 1 in 2000 women above the age of 50 and it is one of the 3 or 4 major reasons for liver transplantation in the U.S. Several trials have been conducted to study the effect of immunosuppressants in PBC including methotrexate (MTX). A randomized trial conparing the effects of 7.5 vs 15 mg per week of oral MTX was started in 1991 and completed in early 1995. 28 patients were randomized to receive one of the two doses and stratified according to the presence or absence of symptoms. Therapy led to decreases in serum alkaline phosphatase and aminotransferase levels and fall to IgM levels to normal. Symptoms improved in 43% of patients and liver histology in 46%. The higher dose was associated with greater improvements in liver histology but the lower dose was effective in a similar percentage of patients. These results indicate that prolonged therapy with adjusted doses of MTX may be effective in ameliorating symptoms and liver pathology in PBC.